rs868042916

Variant names:

• chr4-22747686-C-A
• rs868042916
• ENST00000508166.5:c.677C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-22747686-C-A
• chr4-22747686-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000508166.5(GBA3):​c.677C>A​(p.Ala226Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A226V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBA3 ENST00000508166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

GBA3 (HGNC:19069): (glucosylceramidase beta 3 (gene/pseudogene)) The protein encoded by this gene is a cytosolic enzyme that can hydrolyze several types of glycosides. The enzyme has its highest activity at neutral pH and is predominantly expressed in human liver, kidney, intestine, and spleen. This gene is a polymorphic pseudogene, with the most common allele being the functional allele that encodes the full-length protein. Some individuals contain a single nucleotide polymorphism that results in a premature stop codon in the coding region, and therefore this allele is pseudogenic due to the failure to produce a functional full-length protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20833671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBA3	NR_102355.2	n.756C>A		non_coding_transcript_exon_variant	Exon 3 of 5
GBA3	NR_102357.2	n.678C>A		non_coding_transcript_exon_variant	Exon 3 of 5
GBA3	NR_102356.2	n.365+11478C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBA3	ENST00000508166.5	c.677C>A	p.Ala226Glu	missense_variant	Exon 3 of 5	1		ENSP00000427458.1
GBA3	ENST00000503442.1	c.286+11478C>A		intron_variant	Intron 2 of 2	1		ENSP00000422220.1
GBA3	ENST00000511446.2	c.164C>A	p.Ala55Glu	missense_variant	Exon 3 of 5	2		ENSP00000423754.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	1.9
DANN	Benign	0.49
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.21	T
PrimateAI	Benign	0.29	T
Vest4		0.29
MVP		0.32
GERP RS		-12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs868042916; hg19: chr4-22749309;